One of the current priorities of toxicity testing is the validation of in vitro tests' ability to predict in vivo responses. Whereas mammalian cells in culture have often been shown to mimic in vivo responses to toxic or carcinogenic agents, less is known about non-mammalian species. The ability of non-mammalian in vitro models to predict whole animal responses to toxic or carcinogenic challenges is thought to be at an early stage of validation. Methyl mercury (MeHg) is a highly toxic form of mercury pollution that is widely distributed in both fresh-water and marine environments. The fathead minnow is a widely-used indicator species in toxicity testing. The proposed research is designed to determine if the response of fathead minnow cells in culture is a useful indicator of the toxic action of MeHg in fathead minnow embryos. Both fathead minnow embryos and a cell line derived from fathead minnows will be exposed to a graded series of concentrations of MeHg under controlled conditions. A number of specific toxicological endpoints will be examined for both the in vivo and in vitro exposure. These include: the toxic levels (LC50) of MeHg, the rate of uptake of MeHg, the effect of MeHg on total protein, histopathology and cellular pathology and genotoxicity as measured by sister chromatid exchange (in vitro only). Thus the proposed research will attempt to validate the ability of in vitro testing procedures to predict in vivo responses, and in addition, will give valuable information on the embryotoxic effects of MEHg, a widespread environmental pollutant.